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Heroin drug misusers are a high risk group for disseminated candidiasis.1 Recently, an oral substitute for heroin with oral methadone or high dose sublingual buprenorphine tablets (Subutex) (HDSB) has proved to be effective in management of opioid addiction.2 We report the first four cases of presumed candida endophthalmitis following intravenous injection of HDSB.
A 22 year old man, HIV negative, former heroin misuser, was seen complaining of blurry vision in his right eye. He used HDSB intravenously, after dissolution in saliva. One week following an injection, he presented with a febrile septicaemic syndrome associated with scalp nodules. Funduscopy revealed a moderate vitritis and a white tiny perifoveolar lesion with few white snowballs (Fig 1). The bacterial and fungal cultures from both blood and anterior chamber tap were negative. Treatment was begun with intravenous fluconazole associated with three intravitreal amphotericin B injections (IVT). After 15 days of therapy, he was discharged on oral fluconazole. Ten days later, the endophthalmitis relapsed with development of a second paramacular necrotising lesion. A posterior vitrectomy was performed. The vitreous cultures were negative for Candida albicans. He was treated again with intravenous amphotericin B, along with amphotericin B IVT with success.
A 27 year old man, a former heroin misuser, was receiving HDSB substitution therapy. Occasionally, he injected a preparation of HDSB diluted with preserved lemon juice. Two weeks following such an injection, he developed a skin abscess in which cultures revealed C albicans, posterior cervical lymphadenopathy, nodules of the scalp, and arthritis of the left wrist. Three weeks later he complained of decreased vision in his right eye. Funduscopy revealed a yellowish-white macular lesion and few white snowballs (Fig 2) Treatment was instituted with intravenous amphotericin B and flucytosine but the patient left the hospital against medical advice 4 days later.
A 25 year old man, with history of heroin misuse, was referred for blurry vision and floaters in the right eye. His ocular symptoms started following an intravenous HDSB injection prepared with rotten lemon juice. Funduscopy revealed a parapapillar white lesion and few white vitreous snowballs (Fig 3) Improvement was obtained after 14 days of intravenous fluconazole and amphotericin B IVT.
A 30 year old man, a former heroin misuser, was referred for decreased vision in the left eye. He had been using intravenous HDSB by dissolving the tablets in preserved lemon juice. Ten days earlier, he had a disseminated pustular rash with folliculitis over the chest, shoulders, and back. On funduscopy, there was a 2 + vitritis and a white chorioretinal lesion below the inferotemporal arcade (Fig 4). He improved after a treatment with intravenous amphotericin B rapidly switched to intravenous fluconazole combined with two amphotericin B IVT.
Endogenous candida endophthalmitis diagnosis is usually based on the combination of clinical setting (febrile septicaemia following an intravenous injection, skin typical lesions) and typical fundus lesions.3 Isolation of the fungus from a vitrectomy specimen could provide a definitive diagnosis but this is not routinely performed or required.4 In our cases, the diagnosis of presumed candida endophthalmitis was based on (1) the characteristic clinical setting, (2) the typical ocular involvement that was characterised by creamy-white chorioretinal lesions with white balls and vitritis, and (3) the response to antifungal therapy. Vitrectomy was performed only in one case. It was not performed in three patients because they presented an isolated chorioretinitis or associated with a mild vitritis and a characteristic clinical presentation.5,6 Patients were treated with intravenous amphotericin B or intravenous fluconazole and intravitreal injections of amphotericin B, except in one patient who refused intraocular injections.
In the mid-1980s, in France, an outbreak of candidiasis followed the introduction on the drug market of a new brown heroin.7 The hypothesis that the lemon juice used to dissolve the heroin might have been contaminated with C albicans was demonstrated.8 Our cases also seem to confirm that the fungi probably come from the lemon juice or the patient himself rather than from the buprenorphine itself. Since March 1995, substitution therapy with HDSB tablets (Subutex) is approved for licence in France. Unfortunately, 8% of the patients enrolled in substitution programmes continued to use the intravenous route.9 This drug is now widely prescribed in France. Recently, in Europe, this treatment obtained the authorisation for commercialisation in 13 European countries. Our report demonstrates the need to inform general practitioners, pharmacists, and patients of the risks involved with the intravenous use of substitute agents.